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Human milk proteins, a mixture of whey proteins including caseins, milk fat globule membrane (MFGM) proteins, various peptides, and their amino acids, play a crucial role in infant growth and development, as do non-nutritional bioactive components. The extracellular nicotinamide phosphoribosyltransferase (eNAMPT) or visfatin is a conserved cytokine/enzyme released by many mammalian cells, related to multiple metabolic and immune processes. Few investigations have been reported about detecting visfatin in skimmed milk and the hypothesis of its potential role in regulating infant adiposity through breast milk. Milk samples from a donated human milk bank were analyzed. After milk fractionation by centrifugation, skimmed milk and MFGM were analyzed by SDS-PAGE, MALDI-TOF mass spectrometry ELISA and/or Western blot. The ELISA assay showed a higher visfatin content in raw skimmed milk than in pasteurized samples. Meanwhile, MFGMs revealed higher visfatin levels in pasteurized samples. This is the first time visfatin has been identified associated with MFGM, and these results could suggest an affinity of this molecule for a lipidic environment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Head and neck sarcomas (HNS) constitute a rare and heterogeneous cancer entity. Management remains a challenge due their rarity and different biological behaviour among tens of subtypes. This systematic review aimed to describe HNS global frequency and distribution in adulthood., Methods: A systematic review was performed using PICOTS search strategies for qualitative question and it was written in accordance with PRISMA 2020 Statement. 70,653 publications were identified, and 15 variables were evaluated for a total of 2428 patients., Results: We identified 47 studies from 21 different countries from 5 different continents. Most of studies (83.3%) were performed in single institutions and America and Asia overruled for number of papers included (21 and 10, respectivelly). Osteosarcoma was more frequent, followed by chondrosarcoma, angiosarcoma and malignant fibrous histiocytoma. Early stage accounted for almost 80% of cases; advanced stage prevailed in developing countries. 1783 patients (90.1%) underwent surgery and 780 (39.4%) had adjuvant therapy. 50.8% of patients experienced tumour recurrence and the lowest mortality rate was reported in Europe (29.9%)., Conclusions: HNS holds a relative poor prognosis possibly explained by the heterogeneity of the disease. Treatment of HNS has shown to be highly diverse among different countries, underlining the importance of uniformed treatment guidelines to achieve better patient management and to improve survival outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neurally adjusted ventilatory assist (NAVA) is a respiratory support triggered by the electrical activity of the diaphragm (EAdi). Only few studies evaluated NAVA short-term efficacy and safety in newborns. Aim of this study was to assess efficacy and safety of NAVA in a cohort of newborns and to analyze ventilation parameters helpful to guide weaning., Methods: Thirty-four newborns with respiratory failure were ventilated with synchronized intermittent mandatory ventilation plus pressure-regulated volume control plus pressure support (SIMV(PRVC)+PS) for 12 hours and switched to NAVA until extubation. Ventilator and vital parameters, oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio (S/F), arterialized capillary blood gases (aCBG), and sedatives dose were recorded. The occurrence of reintubation within the first 72 hours, pneumothorax and mortality were evaluated., Results: After 6 hours of NAVA, a significant reduction of FiO2 (0.25 versus 0.32), and peak inspiratory pressure (13 versus 18 mmHg), and a significant increase of S/F (383 versus 316) were found, compared to SIMV(PRVC)+PS. Other ventilation, vital and aCBG parameters were similar in both ventilation modes. During NAVA a significant reduction of sedation was shown. All subjects were successfully extubated guided by EAdi peak during weaning. No reintubation, pneumothorax, or death were recorded., Conclusions: NAVA can be effectively and safely used in neonates. The EAdi peak could be a reliable index to guide the physicians during weaning and extubation.

Background: COVID-19 pandemic caused huge decrease of pediatric admissions to Emergency Department (ED), arising concerns about possible delays in diagnosis and treatment of severe disorders., Methods: Impact of COVID-19 on Pediatric Emergency Room (ICOPER) was a retrospective multicentre observational study including 23 Italian EDs.All the children <18 years admitted, between March 9th and May 3rd 2020 stratified by age, priority code, cause of admission and outcome have been included and compared to those admitted in the same period of 2019.Our objectives were to assess the characteristics of pediatric admissions to EDs since COVID-19 outbreak until the end of lockdown, and to describe the features of critical children., Findings: 16,426 children were admitted in 2020, compared to 55,643 in 2019 (-70·48%). Higher reduction was reported in hospitals without Pediatric Intensive Care Unit (PICU) (-73·38%) than in those with PICU (-64·08%) ( P <0·0001). Admissions with low priority decreased more than critical ones (-82·77% vs. 44·17% respectively; P <0·0001). Reduction of discharged patients was observed both in hospitals with (-66·50%) and without PICU (-74·65%) ( P <0·0001). No difference in the duration of symptoms before admission was reported between 2019 and 2020, with the majority of children accessing within 24 h (55·08% vs. 57·28% respectively; P  = 0·2344)., Interpretation: Admissions with low priority decreased significantly more than those with high priority; we suppose that the fear of being infected in hospital maybe overcame the concerns of caregivers. Compared to 2019, no significant referral delay by caregivers was reported. Our data suggest the need of adaptation of EDs and primary care services to different needs of children during COVID-9 pandemic., Competing Interests: Nothing to disclose., (© 2021 The Author(s).)

Background: A vaccine would be an ideal tool for reducing malaria's impact. PfSPZ Vaccine (radiation attenuated, aseptic, purified, cryopreserved Plasmodium falciparum [Pf] sporozoites [SPZ]) has been well tolerated and safe in >1526 malaria-naive and experienced 6-month to 65-year-olds in the United States, Europe, and Africa. When vaccine efficacy (VE) of 5 doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine was assessed in adults against controlled human malaria infection (CHMI) in the United States and Tanzania and intense field transmission of heterogeneous Pf in Mali, Tanzanians had the lowest VE (20%)., Methods: To increase VE in Tanzania, we increased PfSPZ/dose (9 × 105 or 1.8 × 106) and decreased numbers of doses to 3 at 8-week intervals in a double blind, placebo-controlled trial., Results: All 22 CHMIs in controls resulted in parasitemia by quantitative polymerase chain reaction. For the 9 × 105 PfSPZ group, VE was 100% (5/5) at 3 or 11 weeks (P < .000l, Barnard test, 2-tailed). For 1.8 × 106 PfSPZ, VE was 33% (2/6) at 7.5 weeks (P = .028). VE of dosage groups (100% vs 33%) was significantly different (P = .022). Volunteers underwent repeat CHMI at 37-40 weeks after last dose. 6/6 and 5/6 volunteers developed parasitemia, but time to first parasitemia was significantly longer than controls in the 9 × 105 PfSPZ group (10.89 vs 7.80 days) (P = .039), indicating a significant reduction in parasites in the liver. Antibody and T-cell responses were higher in the 1.8 × 106 PfSPZ group., Conclusions: In Tanzania, increasing the dose from 2.7 × 105 to 9 × 105 PfSPZ increased VE from 20% to 100%, but increasing to 1.8 × 106 PfSPZ significantly reduced VE., Clinical Trials Registration: NCT02613520., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The use of malaria rapid diagnostic tests (RDTs) as a source for nucleic acids that can be analyzed via nucleic acid amplification techniques has several advantages, including minimal amounts of blood, sample collection, simplified storage and shipping conditions at room temperature. We have systematically developed and extensively evaluated a procedure to extract total nucleic acids from used malaria RDTs. The co-extraction of DNA and RNA molecules from small volumes of dried blood retained on the RDTs allows detection and quantification of P. falciparum parasites from asymptomatic patients with parasite densities as low as 1 Pf/µL blood using reverse transcription quantitative PCR. Based on the extraction protocol we have developed the ENAR (Extraction of Nucleic Acids from RDTs) approach; a complete workflow for large-scale molecular malaria surveillance. Using RDTs collected during a malaria indicator survey we demonstrated that ENAR provides a powerful tool to analyze nucleic acids from thousands of RDTs in a standardized and high-throughput manner. We found several, known and new, non-synonymous single nucleotide polymorphisms in the propeller region of the kelch 13 gene among isolates circulating on Bioko Island, Equatorial Guinea.

The bioactive and anti-inflammatory role of human milk components has been recognized; active milk components include soluble forms of Toll-like receptors (TLRs). Preterm babies are more susceptible to infections and may succumb to necrotizing enterocolitis (NEC), a gastrointestinal disease which is exacerbated by an excessive inflammatory response after TLR activation. Here, we investigated the presence of Toll-like receptors TLR1/2/4/6 in colostrum and mature milk of women who delivered before (preterm) or after (term) 37 weeks of gestational age, integrating classical immune-related techniques with proteomic LC-MS/MS analysis. We have detected immunoreactivity for TLRs mostly in preterm samples, even for TLR1 and TLR6, until now not described in human milk. We demonstrated the presence of only TLR2 in the milk fat globule membrane, while the immunoreactivity of TLR1/4/6 was ascribed to crossreaction with some interesting milk proteins sharing leucine-rich repeat domains. These results will provide new insights into the definition of the role of TLRs in intestinal immune regulation of the newborns., Competing Interests: The authors declare that they have no competing interest., (Copyright © 2019 Chiara Cattaneo et al.)

In 2016, there were more cases and deaths caused by malaria globally than in 2015. An effective vaccine would be an ideal additional tool for reducing malaria's impact. Sanaria ® PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (SPZ) has been well tolerated and safe in malaria-naïve and experienced adults in the United States and Mali and protective against controlled human malaria infection with Pf in the United States and field transmission of Pf in Mali, but had not been assessed in younger age groups. We, therefore, evaluated PfSPZ Vaccine in 93 Tanzanians aged 45 years to 6 months in a randomized, double-blind, normal saline placebo-controlled trial. There were no significant differences in adverse events between vaccinees and controls or between dosage regimens. Because all age groups received three doses of 9.0 × 10 5 PfSPZ of PfSPZ Vaccine, immune responses were compared at this dosage. Median antibody responses against Pf circumsporozoite protein and PfSPZ were highest in infants and lowest in adults. T-cell responses were highest in 6-10-year olds after one dose and 1-5-year olds after three doses; infants had no significant positive T-cell responses. The safety data were used to support initiation of trials in > 300 infants in Kenya and Equatorial Guinea. Because PfSPZ Vaccine-induced protection is thought to be mediated by T cells, the T-cell data suggest PfSPZ Vaccine may be more protective in children than in adults, whereas infants may not be immunologically mature enough to respond to the PfSPZ Vaccine immunization regimen assessed.

Jeune syndrome (asphyxiating thoracic dystrophy) is a rare skeletal dysplasia mainly characterized by dystrophy of the thoracic cage. Neurally adjusted ventilatory assist (NAVA) is a respiratory support in which pressure assistance is provided in proportion to and synchronous with the electrical activity of the diaphragm. We present the case of a 4-month-old infant with asphyxiating thoracic dystrophy and respiratory failure successfully ventilated with NAVA. In this case, NAVA improved patient-ventilator synchrony, reducing endotracheal secretion and gastric overdistention. The reduction of breathing effort and the improvement in enteral feeding tolerance and weight gain made the patient eligible for thoracic surgical correction., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: Neurally adjusted ventilatory assist (NAVA) is a novel mode of ventilation that has been demonstrated to improve infant-ventilator interaction, compared to the conventional modes in retrospective and short-term studies., Objectives: To prospectively evaluate the physiologic effects of NAVA in comparison with pressure-regulated volume control (PRVC) in two nonrandomized 12-hour periods., Methods: We studied 14 consecutive intubated preterm neonates receiving mechanical ventilation for acute respiratory failure. Peak airway pressure (Pawpeak), diaphragm electrical activity (EAdi), tidal volume (VT), mechanical (RRmec) and neural (RRneu) respiratory rates, neural apneas, and the capillary arterialized blood gases were measured. The RRmec-to-RRneu ratio (MNR) and the asynchrony index were also calculated. The amount of fentanyl administered was recorded., Results: Pawpeak and VT were greater in PRVC (p < 0.01). Blood gases and RRmec were not different between modes, while RRneu and the EAdi swings were greater in NAVA (p = 0.02 and p < 0.001, respectively). MNR and the asynchrony index were remarkably lower in NAVA than in PRVC (p = 0.03 and p < 0.001, respectively). 1,841 neural apneas were observed during PRVC, with none in NAVA. Less fentanyl was administered during NAVA, as opposed to PRVC (p < 0.01)., Conclusions: In acutely ill preterm neonates, NAVA can be safely and efficiently applied for 12 consecutive hours. Compared to PRVC, NAVA is well tolerated with fewer sedatives., (© 2014 S. Karger AG, Basel.)

Children treated for Langerhans cell histiocytosis (LCH) are at risk for short and long term endocrine sequelae, but biological predictors of specific deficits are not well defined. We evaluated the frequency and progression of LCH-related endocrine deficits during long term follow-up and assessed the ability of dynamic endocrine testing to identify patients at risk for late anterior or posterior pituitary hormone dysfunction. The 17 patients (5 males and 12 females) were followed a median of 10 yr after diagnosis of single system (n = 6) or multisystem (n = 11) disease. Study evaluations, performed a median of 4.1 yr after the diagnosis, comprised pituitary hormone responses to the appropriate challenge, 7-h water deprivation test, 3% hypertonic saline infusion, and magnetic resonance imaging (MRI). The six patients with GH deficiency at the time of evaluation had a significantly lower GH response to GHRH than the other patients [median peak, 7.3 vs. 21.5 micrograms/L (P = 0.03); median area under the curve, 4.7 vs. 13.5 micrograms/L (P = 0.03)]; levels in the latter group did not differ significantly from those in 20 age- and sex-matched controls with constitutional or familial short stature. Two patients who had GH responses to GHRH of 20.6 and 23 ng/mL at 2.8 and 9.5 yr of age developed GH deficiency at 6.5 and 11.2 yr of age, respectively. The TSH response to TRH was less than 10 mU/L in three patients, two of whom later developed central hypothyroidism. ACTH and cortisol responses to CRF, and PRL responses to TRH were normal in all cases, and LH and FSH responses to GnRH were compatible with pubertal stage. Abnormalities in arginine vasopressin responses to water deprivation or hypertonic saline infusion were seen only in four patients who had preexisting diabetes insipidus (DI); one patient who later developed DI had normal findings. On standard MRI, posterior pituitary hyperintensity was absent only in the patients with DI. Pituitary stalk thickening was seen in seven patients, including three who did not have DI and had normal arginine vasopressin responses. Delayed posterior and anterior enhancement on dynamic MRI was present in two patients, both of whom later developed central hypothyroidism. Patients with single system disease had a lower 5-yr probability of LCH reactivation (41% vs. 83% for those with multisystem disease; P = 0.21) and a significantly lower risk of endocrine dysfunction (P = 0.007). In this series, dynamic evaluation of pituitary function was not a useful predictor of late endocrine sequelae, with the possible exception of the progressively decreasing TSH response to TRH. Similarly, a standard MRI was not predictive, although dynamic imaging may be informative regarding evolving pituitary hormone deficiency.